引用本文
王玉波, 徐倩倩, 郭时金, 王艳萍, 张颖, 杨丽梅, 沈志强. 肠致病性大肠杆菌改变肠道上皮细胞极性的研究进展[J]. 中国人兽共患病学报, 2019,35(4): 350-354
WANG Yu-bo, XU Qian-qian, GUO Shi-jin, WANG Yan-ping, ZHANG Ying, YANG Li-mei, SHEN Zhi-qiang. Review on the polarity disruption of intestinal epithelial cells by enteropathogenic Escherichia coli [J]. Chinese Journal of Zoonoses, 2019,35(4): 350-354.  
Doi: 10.3969/j.issn.1002-2694.2019.00.037
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Copyright©2019, 中国人兽共患病学报
中国人兽共患病学报
肠致病性大肠杆菌改变肠道上皮细胞极性的研究进展
王玉波1, 徐倩倩2,3, 郭时金2,3, 王艳萍2,3, 张颖2,3, 杨丽梅2,3, 沈志强2,3
1. 滨州医学院附属医院胸外科,滨州 256600
2. 山东省滨州畜牧兽医研究院 山东省滨州畜禽蜂胶疫苗研究开发推广中心,滨州 256600
3. 山东绿都安特动物药业有限公司,滨州 256600
通讯作者:徐倩倩,Email: qianqian19830125@163.com; ORCID: 0000-0001-7034-7198
收稿日期: 2018-02-12
资助项目: 国家自然科学基金(No. 31402243)和山东省自然科学基金(No. ZR2014CQ012,No. ZR2017MC056)联合资助
摘要

上皮细胞构成了宿主阻止病原微生物入侵机体的生理屏障。细胞间连接,主要是紧密连接,将上皮细胞特殊的顶端和基底外侧膜位点分开,形成极化的上皮细胞,用于维持顶端-基底极性。肠致病性大肠杆菌通过破坏感染位点多种因素导致顶端-基底极性消失,包括上皮细胞屏障结构、黏附和极性蛋白的分布,以及极性复合物。本文主要阐述了紧密连接在维持上皮细胞极性中的作用、肠致病性大肠杆菌对紧密连接的破坏作用、肠致病性大肠杆菌对上皮细胞极性的影响及其作用机制,为肠致病性大肠杆菌作用机制的研究和防御措施提供参考。

关键词: 肠致病性大肠杆菌; 肠道; 上皮细胞; 极性; 紧密连接
中图分类号:S852.61 文献标志码:A 文章编号:1002-2694(2019)04-0350-05
Review on the polarity disruption of intestinal epithelial cells by enteropathogenic Escherichia coli
WANG Yu-bo1, XU Qian-qian2,3, GUO Shi-jin2,3, WANG Yan-ping2,3, ZHANG Ying2,3, YANG Li-mei2,3, SHEN Zhi-qiang2,3
1. Department of Thoracic Surgery, Binzhou Medical College Hospital, Binzhou 256600, China
2. Shandong Binzhou Animal Science and Veterinary Medicine Academy, Shandong Binzhou Research, Development and Promotion Center for Livestock and Poultry Propolis Vaccine, Binzhou 256600, China
3. Shandong Lvdu Ante veterinary drug Industry Co., Ltd, Binzhou 256600, China
Corresponding author: Xu Qian-qian, Email: qianqian19830125@163.com
Fund:Supported by the grant from the National Natural Science Foundation of China (No. 31402243) and the National Science Foundation of Shandong Province, China (Nos. ZR2014CQ012 & ZR2017MC056)
Abstract

Epithelial cells constitute a physical barrier which protects the host from microbial pathogens. Polarized epithelial cells contain distinct apical and basolateral membrane domains separated by intercellular junctions, and the most important were tight junctions, which contribute to the maintenance of apical-basal polarity. Polarity complexes also contribute to the establishment of tight junction(TJ) formation. Enteropathogenic Escherichia coli through dysregulation of multiple factors, including disruption of the intestinal barrier, redistribution of adhesion and polarity proteins, and recruitment of polarity complexes to infection sites, all of which lead to impaired apical-basal polarity and perturbed epithelial TJ barrier function and structure. Here, we review the important role played in intestinal epithelial cells polarity maintenance of tight junctions, impact of enteropathogenic Escherichia coli on the disruption of cell-cell junctions and epithelial polarity, which provide references for the study of enteropathogenic Escherichia coli action mechanism and the corresponding defense methods.

Key words: enteropathogenic Escherichia coli; intestinal; epithelial cell; polarity; tight junction

在发展中国家, 肠致病性大肠杆菌(enteropathogenic Escherichia coli, EPEC)经常引发婴儿腹泻。EPEC感染分为以下几步:第一, 粘附到宿主细胞引起黏附/消除损伤, 并伴随着微绒毛的消失; 第二, 利用Ⅲ 型分泌系统(type III secretion system, T3SS)将细菌效应蛋白传递到宿主细胞内部; 第三, 激动蛋白基座形成[1]。肠道上皮细胞在防御EPEC入侵过程中发挥重要作用。肠道上皮细胞侧膜的顶端部分含有连接复合体, 包括紧密连接(tight junctions, TJs)、黏着连接和细胞桥粒。细胞桥粒和黏着连接机械性地与相邻细胞连接, 而紧密连接在肠腔和单层上皮细胞浆膜侧形成了可调节的屏障(屏障功能)。细胞顶端-基底极性对于细胞功能的发挥具有重要作用, 主要表现在:细胞形态的维持、定向囊泡运输、离子和溶质运输、蛋白和脂类在特异性膜位点的定位等[2, 3]。紧密连接通过限制上皮细胞膜顶端和基底侧的自由活动维持细胞极性, 从而直接帮助水分、电解质和营养的移动(栅栏功能)。本文主要阐述了紧密连接在维持上皮细胞极性中的作用、肠致病性大肠杆菌对紧密连接的破坏作用、肠致病性大肠杆菌对上皮细胞极性的影响及其作用机制。

1 紧密连接与上皮细胞极性

上皮细胞在防御病原微生物入侵中发挥了重要作用。紧密连接位于侧膜顶端部位, 负责填充上皮细胞间的孔隙[4]。TJs通过调节跨上皮水和溶质流动控制细胞渗透性, 通过限制顶端和侧面细胞质膜成分混合维持顶端-基底极性[5]。

TJs由跨膜蛋白和调节蛋白构成。跨膜蛋白包括闭合蛋白、闭锁蛋白、tricellulin、MarvelD3, 和连接粘附分子-A(junctional adhesion molecule-A, JAM-A), 用于维持TJ链结构, 控制细胞渗透性, 调节屏障功能, 参与黏附和免疫系统细胞迁移; 调节蛋白包括正闭锁小带蛋白-1(zonula occludens 1, ZO-1)、ZO-2、ZO-3、扣带蛋白、膜关联鸟苷酸激酶转化蛋白-1(membrane— associated guanylate inverted 1, MAGI-1)、MAGI-3和MUPP-1, 将跨膜蛋白连接于细胞骨架。细胞骨架蛋白(ARP2/3、N-WASP、皮动蛋白和VASP), 激动蛋白调节因子(RhoA、Rac和小GTP酶CDC42家族), 转录因子和非肌肉肌球蛋白II(nonmuscle myosin II, NMII)定位于紧密连接, 调节不同的信号通路[5]。

TJs对于上皮细胞顶端-基底极性的形成和维持至关重要, 通过三种极性复合物控制。Crumbs复合物包括Crumbs(CRB), Lin-7相关蛋白(PALS1)和PALS1相关紧密连接蛋白(PATJ)。Par复合物由分隔缺陷类似物3和6(partitioning defective homologue 3 and6, PAR3/PAR6), 非典型的蛋白激酶C(atypical protein kinase C, aPKC)和CDC42构成。第三个复合物由Scribble、幼虫巨大致死性基因(lethal giant larvae, Lgl)、disc large(Dlg)构成。它们共同维持着细胞顶端-基底极性, 从而维持细胞形态、囊泡定向运输, 离子和电解质转运以及蛋白质和脂质特异性定位于不同的膜位点[2]。

PAR6/aPKC复合物引起了特别关注, PAR6作为支架蛋白与其他所有极性复合物相互作用, 使PKC能够将以此激酶为底物的极性蛋白磷酸化。PAR与CDC42-GTP相互作用激活PKC使PAR3磷酸化, 导致TJ蛋白聚集和细胞极性的建立[6]。PAR6与PALS1和CRB3相互作用, CRB3是aPKC的靶蛋白, 该复合物对于TJ形式非常重要[7]。PAR6与侧面极性蛋白Lgl相互作用, 促使aPKC磷酸化及Lgl从顶膜排出, 使顶端-基底进一步极性化, 促进上皮连接形成[8]。由上可知, TJ和极性蛋白之间存在复杂的相互作用以构成并维持TJ结构和功能以及顶端-基底极性, 保证细胞结构和功能完整。

2 EPEC破坏TJs

EPEC通过Ⅲ 型分泌系统(type III secretion system, T3SS)将细菌效应蛋白传递到宿主肠道上皮细胞, 引发腹泻。EPEC破坏肠道上皮细胞TJ结构, 导致肠道上皮细胞屏障和门控功能改变[9, 10, 11, 12, 13]。EPEC介导的TJs破坏引发宿主细胞多种改变:蛋白-蛋白相互作用的解离; TH蛋白claudin-1、occludin和ZO-1分布紊乱; 侧膜出现异常链导致屏障功能丢失[14]。EPEC效应因子, 特别是EspF、Map、NleA和EspG对TJ混乱方面已有诸多研究。EspF将TJ内occludin重新定位, 减弱了经上皮细胞电阻(transepithelial electrical resistance, TER), 增加了T84单层细胞的通透性[9]。在小鼠感染模型中显示, EspF也能破坏TJs体内结构[15]。EPEC感染小鼠回肠和结肠显示闭锁蛋白呈现显著的再分布和屏障功能的消失, 说明其在EPEC致病性中的作用[9, 11]。

Map调节上皮屏障功能也在EPEC引发腹泻中发挥作用。Map与钠氢交换体调控因子Ⅰ 和Ⅱ (Na+/H+ exchanger regulatory factors I 和II, NHERF1/2)相互作用, 调节肠道离子通道[15]。敲除map可减弱EPEC诱导的Caco-2单层细胞TER下降[10]。Citrobacter rodentium是与EPEC相似的鼠病原, 小鼠感染敲除map的Citrobacter rodentium菌株, 与野生型C. rodentium引起的腹泻相比, 腹泻严重程度明显降低, 说明map在肠道离子和水转运中发挥重要作用[16]。Map在MDCKⅡ 细胞中组成型表达增强了带电荷和不带电荷分子的通透性, 表明门控功能的失效[17]。

NleA使ZO-1和闭锁蛋白重新分配, 引起肠道单层细胞中TER快速降低。NleA结合并抑制COPⅡ 蛋白复合物, 该复合物参与蛋白从内质网到高尔基体的包装和运输[18]。感染C. rodentium鼠模型显示, 去除NleA与COPⅡ 复合物相互作用能够抑制ZO-1和闭锁蛋白的重新分布并减少野生型菌株引起的细胞渗透性增强, 说明NleA能够通过阻止新合成的TJ蛋白到达顶膜来影响TJs[19]。

EspG使TER减少, 调节上皮细胞粒度选择渗透性[12]。EspG破坏微管网络表现在闭锁蛋白在细胞质的蓄积和TJ恢复的延迟, 表明EspG阻止TJ修复[20]。

3 EPEC引起细胞顶端-基底极性消失

EPEC对宿主肠道上皮细胞极性的影响多采用间接研究。Muza-Moons等采用T84肠道上皮细胞证明EPEC感染导致两种底外侧蛋白, β 1-整联蛋白和Na+/K+ ATP酶有序地重新分布到顶端部分。β 1-整联蛋白是一种细胞黏附分子, 参与将极性上皮细胞锚定到底膜。整合素类在极性的形成中发挥了重要作用。

EPEC外膜蛋白和主要黏附因子intimin与EPEC Tir(translocated intimin receptor, Tir)相互作用。intimin能够与宿主蛋白β 1-integrin相互作用, 但这种蛋白位于极性上皮细胞底外侧, 因此不能与肠道EPEC接触。然而EPEC感染促使β 1-integrin移到顶端位置, 从而可以与intimin相互作用。敲除Tir的EPEC感染极性单层上皮细胞对TER没有影响。在极性已改变, β 1-integrin已到达顶端的单层细胞, TER下降与野生型EPEC引起的下降相似, 表明了其在EPEC致病中改变极性的作用[21]。

肠道内有效的离子转运有赖于细胞极性。Na+/K+ATP酶通过底外侧膜转运三种细胞内Na+和两种胞外K+。这种电化学梯度对于小肠和结肠电解质和水转运非常重要[22]。EPEC感染影响多种肠道转运体, 包括钠氢交换体3(NHE3)和腺瘤下调(down regulated in adenoma, DRA), 造成离子和水分丢失, 引发腹泻[23]。EPEC还扰乱Na+/K+ ATP酶在底外侧的定位, 甚至将其他离子转运体和通道重新分配于顶膜位点[14, 21], 可能与EPEC的病理生理学有关。

除了底外侧蛋白重新分布, EPEC感染还导致ZO-1, 闭锁蛋白和claudin-1从TJ区转移到侧膜和细胞质, 这就造成了结构/分子相关性屏障功能的丢失。EPEC感染单层细胞冷冻断裂复型揭示了异常链沿着侧膜表面延伸TJ区下方, 表明TJ区域的普遍性改变。这些结构改变与细胞渗透性增加和TER减少都有关系[14]。基侧膜和TH蛋白的再分布和异常TH链的出现表明顶端-基底极性的消失。EPEC诱导的TJ结构和顶端-基底极性的扰乱使得其他细胞质和膜蛋白自由扩散到非正常细胞位点, 进一步增强了EPEC的致病性。

4 EPEC对Par极性复合物的影响

EPEC感染T84细胞增加PKC-ζ 酶活性, 并促使其从细胞质转移到含有不溶性碎片的膜蛋白[24]。aPKC激酶的激活增加了CDC42与PAR6/aPKC结合, 这是Par极性复合物调节的关键步骤。EPEC效应因子Map激活CDC42 GTPase, 促使丝足的形成[25]和CDC42活化, 可能在改变aPKC活性中也发挥作用。细胞质衔接蛋白14-3-3家族也参与细胞信号传导。PAR3磷酸化后能通过aPKC比较容易地与14-3-3结合, 破坏这种相互作用会导致上皮细胞极性消失, 说明14-3-3/PAR3调节Par极性复合物的活性[26]。在T84单层细胞, EspF与14-3-3ζ 和细胞角蛋白-18(CK-18)相连[27], 支持了EPEC通过其效应因子调节Par复合物的假说。

EspG破坏微管并延迟EPEC感染引发的TJs损伤的修复[20]。EspG与ADP-核糖基化因子(ADP-ribosylation factor, ARF)和P21-激酶(p21-activated kinase, PAK)结合位点RAC/CDC42相结合[28]。PAK家族作用于RAC1和CDC42 GTP酶下游, 调节细胞骨架动力学和细胞移动。虽然EspG与ARF和PAK之间的相互作用对微管损伤没有影响[20], 但其对顶端-基底极性的影响则未见报道。

除了EPEC效应因子对Par极性复合物的直接作用, 可能还存在黏附底座引起的间接作用。例如, EPEC感染过程中, Tir被直接注入宿主细胞, 在细胞内磷酸化并将肌动蛋白聚合物募集于细菌结合位点[29]。Tir与CK-8和CK-18相互作用并将它们募集到EPEC诱导的底座。细胞角蛋白是中间丝(intermediate filaments, IF)的必须部分, 在上皮细胞极化中发挥了重要作用。例如, CK-8基因敲除小鼠显示aPKC下调, 突触融合蛋白3和顶膜蛋白(碱性磷酸酶、蔗糖异麦芽糖酶、囊性纤维化跨膜传导调节因子)消失, 微管紊乱, 离子转运缺陷及离子转运体对细胞隔室脱靶[30]。14-3-3蛋白与CK-8和CK-18结合, CK-18的磷酸化对其与Ser33的结合至关重要[31, 32]。EspF与CK-18相互作用, EPEC感染增加了CK-18的溶解性, 导致EPEC感染上皮细胞IF网络的架构发生剧烈变化。敲除espF能破坏EPEC诱导的CK-18溶解性和IF形态学改变[27]。EspF与14-3-3ζ /CK-18以时间依赖性形成复合物。因此我们推断, EspF通过与14-3-3ζ /CK-18结合在细胞极性破坏中发挥作用。以上结果说明, EPEC效应因子协同作用, 通过在空间上和时间上多角度多步骤的调控的方式破坏细胞极性。

5 展 望

大量研究强调了细胞间连接在顶端-基底极性维持中的作用, 反之亦然, 说明两类分子复合物之间存在交互对话。EPEC对上皮细胞破坏作用的研究较多, 而EPEC对顶端-基底极性的研究较少。我们讨论了EPEC是如何通过异常调节多种因素来改变上皮细胞极性, 包括肠道屏障的破坏、粘附和极性蛋白的重新分布、极性复合物向感染位点的募集, 所有这些都会破坏顶端基底极性。TJs完整性和细胞极性的改变可能是病原体感染性疾病发生过程中的重要步骤。微生物对上皮细胞稳态方面的影响还需进一步研究。

利益冲突:无

编辑:林丹

The authors have declared that no competing interests exist.

参考文献
[1] Lai Y, Rosenshine I, Leong JM, et al. Intimate host attachment: enteropathogenic and enterohaemorrhagic Escherichia coli[J]. Cell Microbiol, 2013, 15(11): 1796-1808. DOI: 10.1111/cmi.12179 [本文引用:1]
[2] Rodriguez-Boulan E, Macara IG. Organization and execution of the epithelial polarity programme[J]. Nat Rev Mol Cell Biol, 2014, 15(4): 225-42. DOI: 10.1038/nrm3775 [本文引用:2]
[3] Tepass U. The apical polarity protein network in Drosophila epithelial cells: regulation of polarity, junctions, morphogenesis, cell growth, and survival[J]. Annu Rev Cell Dev Biol, 2012, 28: 655-85. DOI: 10.1146/annurev-cellbio-092910-154033 [本文引用:1]
[4] Farquhar M, Palade G. Junctional complexes in various epithelia[J]. J Cell Biol, 1963, 17: 375-412. DOI: 10.1083/jcb.17.2.375 [本文引用:1]
[5] Van Itallie C, Anderson J. Architecture of tight junctions and principles of molecular composition[J]. Semin Cell Dev Biol, 2014, 36: 157-165. DOI: 10.1016/j.semcdb.2014.08.011 [本文引用:2]
[6] Suzuki A, Yamanaka T, Hirose T, et al. Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures[J]. J Cell Biol, 2001, 152(6): 1183-1196. DOI: 10.1083/jcb.152.6.1183 [本文引用:1]
[7] Wei Z, Li Y, Iye F, et al. Structural basis for the phosphorylation-regulated interaction between the cyto- plasmic tail of cell polarity protein crumbs and the actin-binding protein moesin[J]. J Biol Chem, 2015, 290(18): 11384-11392. DOI: 10.1074/jbc.M115.643791 [本文引用:1]
[8] Yamanaka T, Horikoshi Y, Sugiyama Y, et al. Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity[J]. Curr Biol, 2003, 13(9): 734-743. DOI: 10.1016/S0960-9822(03)00244-6 [本文引用:1]
[9] Mcnamara BP, Koutsouris A, O’connell CB, et al. Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function[J]. J Clin Invest, 2001, 107(5): 621-629. DOI: 10.1172/JCI11138 [本文引用:3]
[10] Dean P, Kenny B. Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein[J]. Mol Microbiol, 2004, 54(3): 665-675. DOI: 10.1111/j.1365-2958.2004.04308.x [本文引用:2]
[11] Guttman JA, Li Y, Wickham ME, et al. Attaching and effacing pathogen-induced tight junction disruption in vivo[J]. Cell Microbiol, 2006, 8(4): 634-645. DOI: 10.1111/j.1462-5822.2005.00656.x [本文引用:2]
[12] Tomson FL, Viswanathan VK, Kanack KJ, et al. Enteropathogenic Escherichia coli EspG disrupts microtubules and in conjunction with Orf3 enhances perturbation of the tight junction barrier[J]. Mol Microbiol, 2005, 56(2): 447-464. DOI: 10.1111/j.1365-2958.2005.04571.x [本文引用:2]
[13] Matsuzawa T, Kuwae A, Abe A. Enteropathogenic Escherichia coli type III effectors EspG and EspG2 alter epithelial paracellular permeability[J]. Infect Immun, 2005, 73(10): 6283-6289. DOI: 10.1128/IAI.73.10.6283-6289.2005 [本文引用:1]
[14] Muza-Moons MM, Schneeberger EE, Hecht GA. Enteropathogenic Escherichia coli infection leads to appearance of aberrant tight junctions strand s in the lateral membrane of intestinal epithelial cells[J]. Cell Microbiol, 2004, 6(8): 783-793. DOI: 10.1111/j.1462-5822.2004.00404.x [本文引用:3]
[15] Tapia R, Kralicek SE, Hecht GA. EPEC effector EspF promotes Crumbs3 endocytosis and disrupts epithelial cell polarity[J]. Cell Microbiol, 2017, 19(11). DOI: 10.1111/cmi.12757 [本文引用:2]
[16] Martinez E, Schroeder GN, Berger CN, et al. Binding to Na(+) /H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH[J]. Cell Microbiol, 2010, 12(12): 1718-1731. DOI: 10.1111/j.1462-5822.2010.01503.x [本文引用:1]
[17] Singh AP, Aijaz S. Generation of a MDCK cell line with constitutive expression of the Enteropathogenic E. coli effector protein Map as an in vitro model of pathogenesis[J]. Bioengineered, 2015, 6(6): 335-341. DOI: 10.1080/21655979.2015.1096456 [本文引用:1]
[18] Kim J, Thanabalasuriar A, Chaworth-Musters T, et al. The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function[J]. Cell Host Microbe, 2007, 2(3): 160-171. DOI: 10.1016/j.chom.2007.07.010 [本文引用:1]
[19] Thanabalasuriar A, Kim J, Gruenheid S. The inhibition of COPII trafficking is important for intestinal epithelial tight junction disruption during enteropathogenic Escherichia coli and Citrobacter rodentium infection[J]. Microbes Infect, 2013, 15(10-11): 738-744. DOI: 10.1016/j.micinf.2013.05.001 [本文引用:1]
[20] Glotfelty LG, Zahs A, Iancu C, et al. Microtubules are required for efficient epithelial tight junction homeostasis and restoration[J]. Am J Physiol Cell Physiol, 2014, 307(3): C245-254. DOI: 10.1152/ajpcell.00336.2013 [本文引用:3]
[21] Muza-Moons MM, Koutsouris A, Hecht G. Disruption of cell polarity by enteropathogenic Escherichia coli enables basolateral membrane proteins to migrate apically and to potentiate physiological consequences[J]. Infect Immun, 2003, 71(12): 7069-7078. DOI: 10.1128/IAI.71.12.7069-7078.2003 [本文引用:2]
[22] Charney AN, Kinsey MD, Myers L, et al. Na+-K+-activated adenosine triphosphatase and intestinal electrolyte transport. Effect of adrenal steroids[J]. J Clin Invest, 1975, 56(3): 653-660. DOI: 10.1172/JCI108135 [本文引用:1]
[23] Gill RK, Borthakur A, Hodges K, et al. Mechanism underlying inhibition of intestinal apical Cl/OH exchange following infection with enteropathogenic E. coli[J]. J Clin Invest, 2007, 117(2): 428-437. DOI: 10.1172/JCI29625 [本文引用:1]
[24] Savkovic SD, Koutsouris A, Hecht G. PKC zeta participates in activation of inflammatory response induced by enteropathogenic E. coli[J]. Am J Physiol Cell Physiol, 2003, 285(3): C512-521. DOI: 10.1152/ajpcell.00444.2002 [本文引用:1]
[25] Huang Z, Sutton SE, Wallenfang AJ, et al. Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics[J]. Nat Struct Mol Biol, 2009, 16(8): 853-860. DOI: 10.1038/nsmb.1647 [本文引用:1]
[26] Izaki T, Kamakura S, Kohjima M, et al. Phosphorylation-dependent binding of 14-3-3 to Par3beta, a human Par3-related cell polarity protein[J]. Biochem Biophys Res Commun, 2005, 329(1): 211-218. DOI: 10.1016/j.bbrc.2005.01.115 [本文引用:1]
[27] Viswanathan VK, Lukic S, Koutsouris A, et al. Cytokeratin 18 interacts with the enteropathogenic Escherichia coli secreted protein F (EspF) and is redistributed after infection[J]. Cell Microbiol, 2004, 6(10): 987-997. DOI: 10.1111/j.1462-5822.2004.00416.x [本文引用:2]
[28] Germane KL, Spiller BW. Structural and functional studies indicate that the EPEC effector, EspG, directly binds p21-activated kinase[J]. Biochemistry, 2011, 50(6): 917-919. DOI: 10.1021/bi1020138 [本文引用:1]
[29] Goosney DL, De Grado M, Finlay BB. Putting E. coli on a pedestal: a unique system to study signal transduction and the actin cytoskeleton[J]. Trends Cell Biol, 1999, 9(1): 11-14. DOI: 10.1016/S0962-8924(98)01418-4 [本文引用:1]
[30] Mashukova A, Oriolo AS, Wald FA, et al. Rescue of atypical protein kinase C in epithelia by the cytoskeleton and Hsp70 family chaperones[J]. J Cell Sci, 2009, 122(Pt 14): 2491-2503. DOI: 10.1242/jcs.046979 [本文引用:1]
[31] Liao J, Omary MB. 14-3-3 proteins associate with phosphorylated simple epithelial keratins during cell cycle progression and act as a solubility cofactor[J]. J Cell Biol, 1996, 133(2): 345-357. DOI: 10.1083/jcb.133.2.345 [本文引用:1]
[32] Ku NO, Michie S, Resurreccion EZ, et al. Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression[J]. Proc Natl Acad Sci U S A, 2002, 99(7): 4373-4378. DOI: 10.1073/pnas.072624299 [本文引用:1]